Fluid flow systems or assemblies that are pre-sterilized and/or pre-assembled are used in a wide variety of medical and non-medical applications. Medical applications may include, for example, administration of medical fluids to a patient for therapeutic and/or diagnostic purposes, blood and/or blood component or other cell collection or processing, dialysis and other medical procedures. Non-medical applications for such systems or assemblies may include, for example, pharmaceutical manufacturing and cell processing. In the medical field in particular, such flow systems commonly employ one or more pre-filled containers or other sources of medical fluid or agent and an associated fluid flow circuit or system (sometimes called a tubing set) containing the necessary flow tubing, valves, flow controllers, process chambers and the like to carry out the particular procedure, either alone or in cooperation with a reusable controller or other device. It is not unusual, for example, for a medical fluid flow system to include or be used in association with a container of a suitable drug, saline, anticoagulant, dextrose solution, sterile water, cell preservative or the like, to name just a few examples.
Such a fluid flow system can, however, pose manufacturing or assembly challenges for different reasons. One reason can be that the pre-filled containers of medical liquid, powder or other agent that is administered to the patient or otherwise employed in the medical fluid flow system, require different sterilization techniques than other portions of the fluid flow system. For example, empty plastic tubing, containers, flow control devices and/or processing devices or chambers, which do not contain any substantial amount of liquid or other agent, may be sterilized with gamma or electron beam (e-beam) radiation or by exposure to a sterilizing gas, e.g., ethylene oxide. However, gas sterilization would be ineffective to sterilize an agent, such as a liquid, powder or drug, contained in a sealed container, and exposing the agent to ionizing radiation may degrade or otherwise have a deleterious effect on the agent. Also, there may be situations where different portions of a sterile fluid flow system, even though suitable for the same sterilization process, are separately manufactured and sterilized for other reasons and then subsequently assembled in a sterile manner.
In addition sterile connections often need to be made on site, by the end user, e.g., at the location where the fluid flow systems are being used to treat patients or collect or process blood, or blood components, or biologic materials, or in other therapeutic or diagnostic procedures. For example, it may be desired to join a fluid source, filters, tubing or the like to other apparatus without compromising the sterility of any pre-sterilized components or parts of the assembly.
As a result of these various needs, a number of different approaches have been used in assembling sterile fluid flow systems. For example, one technique for manufacturing such systems employs the use of a sterile docking system, such as a device disclosed in U.S. Pat. No. 4,157,723. As illustrated there, the sterile docking system comprises a pair of mating members, each having a facing membrane. One of the mating members is connected to a pre-sterilized container of liquid, drug or other agent and the other mating member is attached to a pre-sterilized fluid flow system, which may include one or more empty containers. After the two members are joined, the docking system is exposed to radiant energy, causing the membranes to melt and form a sterile fluid pathway through the mating members. Fluid may then be transferred from the initial container into an empty container in the fluid flow system, and the flow path sealed and severed. The initial container and mating members are then discarded. While this works satisfactorily, it entails multiple manufacturing steps of transferring solution from one container to another in a sterile manner and the associated quality control procedures with such a step. It also requires the disposal of a portion of the product with increased product and waste cost.
Another technique for assembling medical fluid flow assemblies that have different pre-sterilized portions, such as the type requiring different sterilization processes, employs an electron beam. This technique, as described in U.S. Pat. No. 5,009,645, requires a manufacturing procedure employing an electron beam or the like to sterilize isolated portions of subassemblies after they have been joined together. After the isolated regions are joined and sterilized, clamps or frangible closures which isolate the regions may then be opened to allow for direct sterile communication between the subassemblies. Such a procedure and the use of e-beam or similar radiation, of course, requires a substantial investment in manufacturing equipment as well as additional procedures and safeguards during manufacture.
To avoid the use of more complicated manufacturing processes, it has also been disclosed to use sterilizing filters on the inlet flow line that couples a pre-sterilized liquid container or the like to a separately sterilized fluid flow tubing system. Such an arrangement is illustrated in U.S. Pat. No. 4,978,446. In the approach in the '446 patent, however, the medical personnel are required to manually join the fluid flow tubing system to the fluid container, such as by spiking the fluid container with a piercing member associated with the fluid flow system. In addition to the administrative requirements for individually ordering, storing and prescribing solutions and disposable flow systems or sets, there is the added possibility of errors, such as by connection of a container of an incorrect liquid or other agent or an improper flow system to be used in association with the procedure.
Also, there is a known device commonly referred to as sterile tubing welder that is marketed by Terumo Medical Corporation as the “SCD Device.” That device uses a heated wafer to slice and melt the ends of tubing, which are joined together after the wafer is removed. Aspects of this device are disclosed in various patents, including U.S. Pat. Nos. 4,753,697, 5,158,630 and 5,156,701. Although widely used, particularly as an “on-site” tool to allow users to assemble a system in such configuration as they desire, this device requires the use of expensive wafers that are replaced after each splice.
Sterile connection systems using a melting process are found in WO 2008/131442 A2 and WO 82/02528 and a sterile connection system using a movable internal wall and limited sterilization is found in U.S. Pat. No. 4,030,494.
Accordingly, there remains a significant need for advancements in this field.